Human placental phosphatase has an unusually high degree of allelic variation. One possible explanation for this variation is that there is "natural selection" against rare variant enzymes, possibly involving spontaneous abortion and complications of pregnancy. In order to test this interesting possibility, two approaches are being pursued in this grant. In the first, screening of placentae from normal and complicated pregnancies is being carried out to determine whether a positive correlation exists between rare variants and complications. In the second, biochemical studies are being carried out on the rare "D-variant" in comparison with more common variant enzymes. These studies include the enzyme kinetics of specific inhibitors (L-leucine and its derivatives) and comparison of the structure of the "A" and "B" forms of placental phosphatase. The goal of the biochemical studies is to attempt to determine the biochemical function of the enzyme.